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Both hyperthyroidism and elevated plasma branched chain amino acids (BCAA) are associated with insulin resistance. BCAA utilization and clearance relative to thyroid status changes remains unclear. We investigate amino acids changes, specifically BCAA, during the transition from hyperthyroidism to euthyroidism, and the impact of active brown adipose tissue (BAT) on the metabolic effects of BCAA. Newly diagnosed Graves' disease participants were recruited. Hyperthyroidism was treated via a titration dosing regimen of thionamide anti-thyroid drug to establish euthyroidism over 12-24 weeks. All underwent energy expenditure (EE) measurement within a chamber calorimeter, 18F-fluorodeoxyglucose (18F-FDG) positron-emission tomography/magnetic resonance (PET/MR) imaging and plasma amino acids measurement during hyperthyroidism and euthyroidism. PET BAT maximum standardized uptake value (SUVmax), SUVmean and MR supraclavicular fat fraction (FF) quantified BAT activity. Twenty-two patients completed the study. Plasma BCAA level was significantly reduced in BAT-positive but not in BAT-negative patients during the transition from hyperthyroidism to euthyroidism. Plasma valine but not leucine and isoleucine correlated positively with insulin and HOMA-IR in hyperthyroidism. Plasma valine, leucine and isoleucine correlated with insulin and HOMA-IR in euthyroidism. Plasma valine correlated with insulin and HOMA-IR in BAT-negative but not in BAT-positive participants in both hyperthyroid and euthyroid state. However, the change (i.e. decrease) in plasma valine concentration from hyperthyroid to euthyroid state was affected by BAT-status. BAT utilizes and promotes BCAA plasma clearance from hyperthyroid to euthyroid state. Active BAT can potentially reduce circulating BCAA and may help to ameliorate insulin resistance and improve metabolic health.Clinical trial registration: The trial was registered at clinicaltrials.gov as NCT03064542. National Medical Research Council (NMRC) Published version The study was supported by the National Medical Research Council Award grant. Grant number: NMRC/ CSA-INV/0003/2015.

Background Branched chain amino acids (BCAA) can impair insulin signaling, and cardiac insulin resistance can occur in the failing heart. We, therefore, determined if cardiac BCAA accumulation occurs in patients with dilated cardiomyopathy (DCM), due to an impaired catabolism of BCAA, and if stimulating cardiac BCAA oxidation can improve cardiac function in mice with heart failure. Method For human cohorts of DCM and control, both male and female patients of ages between 22 and 66 years were recruited with informed consent from University of Alberta hospital. Left ventricular biopsies were obtained at the time of transplantation. Control biopsies were obtained from non-transplanted donor hearts without heart disease history. To determine if stimulating BCAA catabolism could lessen the severity of heart failure, C57BL/6J mice subjected to a transverse aortic constriction (TAC) were treated between 1 to 4-week post-surgery with either vehicle or a stimulator of BCAA oxidation (BT2, 40 mg/kg/day). Result Echocardiographic data showed a reduction in ejection fraction (54.3 ± 2.3 to 22.3 ± 2.2%) and an enhanced formation of cardiac fibrosis in DCM patients when compared to the control patients. Cardiac BCAA levels were dramatically elevated in left ventricular samples of patients with DCM. Hearts from DCM patients showed a blunted insulin signalling pathway, as indicated by an increase in P-IRS1ser636/639 and its upstream modulator P-p70S6K, but a decrease in its downstream modulators P-AKT ser473 and in P-GSK3β ser9. Cardiac BCAA oxidation in isolated working hearts was significantly enhanced by BT2, compared to vehicle, following either acute or chronic treatment. Treatment of TAC mice with BT2 significantly improved cardiac function in both sham and TAC mice (63.0 ± 1.8 and 56.9 ± 3.8% ejection fraction respectively). Furthermore, P-BCKDH and BCKDK expression was significantly decreased in the BT2 treated groups. Conclusion We conclude that impaired cardiac BCAA catabolism and insulin signaling occur in human heart failure, while enhancing BCAA oxidation can improve cardiac function in the failing mouse heart. Electronic supplementary material The online version of this article (10.1186/s12933-019-0892-3) contains supplementary material, which is available to authorized users.

The loss of fat-free mass (FFM) that occurs during weight loss secondary to low-calorie diet can lead to numerous and deleterious consequences. We performed a review to evaluate the state of the art on metabolic and nutritional correlates of loss of fat free mass during low calorie diet and treatment for maintaining fat free mass.This review included 44 eligible studies. There are various diet strategies to maintain FFM during a low-calorie diet, including adoption of a very low carbohydrate ketogenic diet (VLCKD) and taking an adequate amount of specific nutrients (vitamin D, leucine, whey protein).Regarding the numerous and various low-calorie diet proposals for achieving weight loss, the comparison of VLCKD with prudent low-calorie diet found that FFM was practically unaffected by VLCKD. There are numerous possible mechanisms for this, involving insulin and the insulin-like growth factor-1-growth hormone axis, which acts by stimulating protein synthesis.Considering protein and amino acids intake, an adequate daily intake of leucine (4 g/d) and whey protein (20 g/d) is recommended. Regarding vitamin D, if the blood vitamin D has low values (30 ng/mL), it is mandatory that adequate supplementation is provided, specifically calcifediol, because in the obese patient this form is recommended to avoid seizure in the adipose tissue; 3 to 4 drops/d or 20 to 30 drops/wk of calcifediol are generally adequate to restore normal 25(OH)D plasma levels in obese patients.

A variety of sodium-substrate cotransport systems are known in bacteria. Sodium enters the cell down an electrochemical concentration gradient. There is obligatory coupling between the entry of the ion and the entry of substrate with a stoichiometry (in the cases studied) of 1:1. Thus, the downhill movement of sodium ion into the cell leads to the accumulation of substrate within the cell. The melibiose carrier of Escherichia coli is perhaps the most carefully studied of the sodium cotransport systems in bacteria. This carrier is of special interest because it can also use protons or lithium ions for cotransport. Other sodium cotransport carriers that have been studied recently are for proline, glutamate, serine-threonine, citrate and branched chain amino acids.

Twenty-two amino acid substitutions at seven conserved amino acid residues in the acetohydroxyacid synthase (AHAS) gene have been identified to date that confer target-site resistance to AHAS-inhibiting herbicides in biotypes of field-evolved resistant weed species. However, the effect of resistance mutations on AHAS functionality and plant growth has been investigated for only a very few mutations. This research investigates the effect of various AHAS resistance mutations in Lolium rigidum on AHAS functionality and plant growth. The enzyme kinetics of AHAS from five purified L. rigidum populations, each homozygous for the resistance mutations Pro-197-Ala, Pro-197-Arg, Pro-197-Gln, Pro-197-Ser or Trp-574-Leu, were characterized and the pleiotropic effect of three mutations on plant growth was assessed via relative growth rate analysis. All these resistance mutations endowed a herbicide-resistant AHAS and most resulted in higher extractable AHAS activity, with no-to-minor changes in AHAS kinetics. The Pro-197-Arg mutation slightly (but significantly) increased the Km for pyruvate and remarkably increased sensitivity to feedback inhibition by branched chain amino acids. Whereas the Pro-197-Ser and Trp-574-Leu mutations exhibited no significant effects on plant growth, the Pro-197-Arg mutation resulted in lower growth rates. It is clear that, at least in L. rigidum, these five AHAS resistance mutations have no major impact on AHAS functionality and hence probably no plant resistance costs. These results, in part, explain why so many Pro-197 AHAS resistance mutations in AHAS have evolved and why the Pro-197-Ser and the Trp-574-Leu AHAS resistance mutations are frequently found in many weed species. Fil: Yu, Qin. University of Western Australia; Australia Fil: Han, Heping. University of Western Australia; Australia Fil: Vila Aiub, Martin Miguel. University of Western Australia; Australia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Fisiológicas y Ecológicas Vinculadas a la Agricultura. Universidad de Buenos Aires. Facultad de Agronomía; Argentina Fil: Powles, Stephen B.. University of Western Australia; Australia

Plasma amino acid abnormalities in rats treated with large doses of sake and whisky for 3 days were investigated under adequate nutritional conditions. A significant decrease in plasma branched-chain amino acid (BCAA) levels was observed in sake- but not whisky-treated rats. However, known factors affecting BCAA levels, such as serum insulin and plasma glucagon levels ahd BCAA-metabolizing enzyme (BCAA transaminase and branched chain alpha-ketoacid dehydrogenase) activities in the liver and skeletal muscle, were not significantly altered in the sake group. Furthermore, ethanol-metabolizing enzyme (alcohol and aldehyde dehydrogenases and the microsomal ethanol-oxidizing system) activities in the liver were not altered in the sake group. Other mechanisms need to be considered for explaining the diminished levels of plasma BCAA in sake-treated rats.

A new nutritional product (SF-1008C) containing a high proportion of branched chain amino acids (BCAA) and low proportion of aromatic amino acids (AAA) and methionine was tested to see its effect on the impaired protein metabolism and abnormal nutritional state frequently observed in patients with advanced liver cirrhosis. A sharp increase in plasma BCAA levels and fall of AAA and methionine levels were found following the administration of an SF-1008C-supplemented diet to healthy controls and cirrhotic patients, which the BCAA levels increased only slightly following an isocaloric control diet. Blood ammonia levels increased within the normal range transiently following the diets. The SF-1008C-supplemented diet was given for 2 weeks to cirrhotic patients with histories of hepatic encephalopathy, who were taking a low-protein diet because of hyperammonemia. Serum prealbumin levels, nitrogen balance, molar ratio of plasma BCAA/phenylalanine and tyrosine, the number connection test and electroencephalograms improved during the period of the experimental diet. The results, therefore, indicate that a BCAA-supplemented diet is well tolerated by patients with advanced cirrhosis and useful for treatment of impaired protein metabolism. Furthermore, this product is beneficial in preventing hepatic encephalopathy in cirrhotics.

Plant metabolism is perturbed by various abiotic stresses. As such the metabolic network of plants must be reconfigured under stress conditions in order to allow both the maintenance of metabolic homeostasis and the production of compounds that ameliorate the stress. The recent development and adoption of metabolomics and systems biology approaches enable us not only to gain a comprehensive overview, but also a detailed analysis of crucial components of the plant metabolic response to abiotic stresses. In this review we introduce the analytical methods used for plant metabolomics and describe their use in studies related to the metabolic response to water, temperature, light, nutrient limitation, ion and oxidative stresses. Both similarity and specificity of the metabolic responses against diverse abiotic stress are evaluated using data available in the literature. Classically discussed stress compounds such as proline, γ-amino butyrate and polyamines are reviewed, and the widespread importance of branched chain amino acid metabolism under stress condition is discussed. Finally, where possible, mechanistic insights into metabolic regulatory processes are discussed. Electronic supplementary material The online version of this article (doi:10.1007/s00018-012-1091-5) contains supplementary material, which is available to authorized users.

The prevention of hepatic encephalopathy by the intravenous infusion of a branched chain amino acid (BCAA)-enriched solution was investigated in methionine and ammonium acetate-treated rats whose liver was already injured with carbon tetrachloride. A BCAA-enriched solution protected the rats from entering a coma. The brain BCAA contents became higher, and the brain methionine and tyrosine levels and the ratio of glutamine to glutamic acid in the brain diminished after administering the BCAA-enriched solution.